Flexible polymer needle catheter

ABSTRACT

A catheter device having an elongated tubular member with a proximal end and a distal end, and a needle disposed near the distal end. In one embodiment, the needle has a rigid, penetrating tip coupled to a flexible portion by an overlapping joint. The flexible portion enables the needle to bend to a penetrating angle relative to the distal end of the elongated tubular member and penetrate a body tissue without kinking.

This application is a divisional application of U.S. patent applicationSer. No. 10/263,640, filed Oct. 2, 2002 now U.S. Pat. No. 6,855,124.

FIELD OF THE INVENTION

The invention, in one embodiment, relates generally to catheters, andmore particularly, in one embodiment, to percutaneous needle catheters.

BACKGROUND OF THE INVENTION

Atherosclerosis, a process in which the walls of the arteries thickendue to the accumulation of plaque in the blood vessels, is the cause ofmost coronary artery disease (CAD) that can result in heart attacks,strokes, or inadequate circulation to the extremities. Arterialocclusions caused by plaque accumulation may necessitate major invasivesurgery, such as a coronary by-pass procedure. However, less invasive,percutaneous methods may be an alternative in treating atherosclerosis.For example, percutaneous transluminal coronary angioplasty (PTCA)involves advancing a balloon catheter through a body lumen to a targettreatment site. In one example, a small incision is made near thefemoral artery to insert the catheter, which is then advanced to aplaque area in the coronary artery. The catheter has a deflated balloonnear a distal end, and the balloon is positioned across the plaque. Oncein position, the balloon is inflated to crack or flatten the plaque,thereby restoring the normal patency of the blood vessel. The balloon isthen deflated so that the catheter can be removed, allowing blood flowto resume through the dilated blood vessel.

Percutaneous delivery of therapeutic agents may also be performed aloneor in combination with PCTA treatments. Needle catheters are one type ofpercutaneous medical devices that may be used to deliver a therapeuticagent or drug to treat diseases associated with CAD. However, thetortuous nature of vessels in the body make it difficult for advancing aneedle catheter to a target treatment site. Furthermore, to optimize atherapeutic drug treatment, the active drug or biologic agent may needto be injected directly into a vessel wall. This type of drug deliveryrequires a high level of accuracy because the proper point in the vesselwall should be penetrated. In another type of drug delivery treatmentwith a needle catheter, biologically active agents may be delivered to acardiac structure (such as into an intraventricular wall), which alsorequires that the needle catheter be flexible enough to navigate andadvance through body vessels and to the heart. U.S. Pat. No. 6,093,177describes one type of flexible catheter that may be used within a heartchamber.

FIG. 1 illustrates an example of a prior art needle catheter. The needletip is connected to a needle shaft that may be steered and moved from aretracted position within a sleeve and an extended position past adistal end of the sleeve to penetrate a body tissue. The needle shaftmay have a tubular lumen so that a drug or biologic agent may beinjected through the needle tip to the body tissue. The needle tip(along with the needle shaft) is usually a continuous piece of metallicmaterial to provide sufficient strength and support to prevent kinkingduring advancement through a tortuous vessel and tissue penetration.

One problem with a metallic needle and/or needle shaft is that it maynot provide the necessary flexibility to navigate through tortuous bodyvessels, which are characteristic of arterial regions. Because of thelack of flexibility of these needle catheters, it may be difficult todeliver biologic agents deep within the arterial regions of the body.Moreover, it may be even more difficult to bend the penetrating tip ofthe needle to pierce a vessel wall to optimize drug delivery treatment.

SUMMARY OF THE INVENTION

A catheter device having an elongated tubular member with a proximal endand a distal end, and a needle disposed near the distal end isdescribed. In one embodiment, the needle has a rigid, penetrating tipcoupled to a flexible portion by an overlapping joint. The flexibleportion enables the needle to bend to a penetrating angle relative tothe distal end of the elongated tubular member and penetrate a bodytissue without kinking.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention is illustrated by way of example, and notlimitation, in the figures of the accompanying drawings in which:

FIG. 1 illustrates a prior art needle catheter.

FIG. 2 illustrates an exemplary embodiment of a needle for use with aneedle catheter having a rigid tip portion coupled to a flexibleportion.

FIG. 3A illustrates an exemplary embodiment of an overlapping joint of aneedle for use with a needle catheter.

FIG. 3B illustrates another exemplary embodiment of an overlapping jointof a needle for use with a needle catheter.

FIG. 4A illustrates an exemplary embodiment of a flexible portion of aneedle reinforced with braided wire for use with a needle catheter.

FIG. 4B illustrates another exemplary embodiment of a flexible portionof a needle reinforced with wire coil for use with a needle catheter.

FIG. 5 illustrates an exemplary embodiment of a needle catheter.

FIG. 6 illustrates another exemplary embodiment of a needle catheter.

FIG. 7 illustrates another exemplary embodiment of a needle catheter.

FIG. 7A illustrates a cross sectional view of the needle catheterillustrated in FIG. 7.

FIGS. 8A-8D illustrate an exemplary method of delivering a biologicagent to a body tissue using a flexible needle catheter.

FIG. 9 illustrates an exemplary method of delivering a biologic agent toan intraventricular wall with one embodiment of a flexible needlecatheter.

DETAILED DESCRIPTION

In the following description, numerous specific details are set forthsuch as examples of specific, components, processes, etc. in order toprovide a thorough understanding of various embodiment of the presentinvention. It will be apparent, however, to one skilled in the art thatthese specific details need not be employed to practice variousembodiments of the present invention. In other instances, well knowncomponents or methods have not been described in detail in order toavoid unnecessarily obscuring various embodiments of the presentinvention. The term “coupled” as used herein means connected directly orindirectly through one or more intervening structures or elements.

Various embodiments of a flexible needle catheter and methods for usinga needle catheter are described. The needle catheter, in one embodiment,may be used to delivery a bioactive agent or therapeutic drugpercutaneously by advancing the needle to a target treatment region(e.g., an arterial wall or within a cardiac chamber). As used herein,the terms “bioactive agent,” “therapeutic agent,” or “therapeutic drug”are used interchangeably to refer to substances that are known to oneskilled in the art to treat various types of diseases or ailments. Thesesubstances may take the form of fluids, solids (e.g., microcapsules) orany other form that may be injected with a needle catheter.

In one embodiment, the needle of the needle catheter may have a rigid,penetrating tip coupled to flexible portion by a first overlappingjoint. The penetrating tip of the needle may be a metallic material suchas stainless steel. The flexible portion of the needle may be a polymeror polymer blend to enable the needle to bend to a penetrating anglerelative to the distal end of the catheter so that the penetrating tipmay pierce a body tissue without kinking. In another embodiment, theflexible portion of the needle may be coupled to a needle shaft by asecond overlapping joint. The needle shaft may be may be metallic orpolymer based. Alternatively, the flexible portion coupled to the needletip portion may be reinforced with embedded braided or coiled wire(s)embedded within the walls of the flexible portion.

FIG. 2 illustrates one embodiment of a needle of the present inventionthat may be used in a needle catheter. Needle 200 has tip portion 210,flexible portion 220, needle shaft portion 230, first overlapping joint240 and second overlapping joint 245. In one embodiment, needle 200 maybe part of a needle catheter assembly in which needle 200 may be thedisposed near a distal end of the catheter. Needle 200 is illustrated ina partially extended position from sheath 250. In a retracted position(not shown), tip portion 210 would be completely housed within sheath250. For example, the needle would remain in the retracted positionuntil it has advanced to the target region within a patient's body, justbefore extending to penetrate a body tissue and inject a biologicallyactive agent into the body tissue (discussed in greater detail withrespect to FIGS. 8A-8D).

Needle 200 has tip portion 210, flexible portion 220, and needle shaftportion 230 all coupled together to form one continuous needlestructure. In one embodiment, needle 200 may be hollow with a beveledtip portion 210 to penetrate, for example, a body tissue and deliver abiologic agent. Tip portion 210 is coupled to flexible portion 220 byforming a first overlapping joint 240 near a distal end of needle 200.Flexible portion 220 is coupled to needle shaft 230 by forming a secondoverlapping joint 245 proximal to first overlapping joint 240. Thecombined tip portion 210 and flexible portion 220 of needle 200 may havea length in a range from 10 to 20 millimeters. In one embodiment, needle200 has needle tip portion 210 of length 5 millimeters with an innerdiameter of 20 mils and an outer diameter of 27 mils. Flexible tubing220 has a length of 10 millimeters with an inner diameter of 8.7 milsand an outer diameter of 14.2 mils. The length of first and secondoverlap joints may be between 4-8 millimeters.

Tip portion 210 is made of a material rigid enough to penetrate a bodytissue. In one embodiment, tip portion 210 may be a stainless steel tip(SST). In another embodiment, tip portion 210 may be made of comparablemetallic material to that of stainless steel known to one of skill inthe art, including shape memory alloys (e.g., nickel-titanium, alsoreferred to as “NiTi” or “NiTinol”). In another alternative embodiment,tip portion 210 may be made of ceramic or material which are compatiblewith MRI (magnetic resonance imaging) in that the materials do notintroduce artifacts in MRI images.

Flexible portion 220 enables tip portion 210 of needle 200 to bend to anecessary penetration angle to pierce a target body tissue. Flexibleportion 220 may be made of any high modulus/high strength polymer gradeor polymer blend. Grade, formulations, or blends of polymers that may beused for flexible member 220 include, but are not limited to polyimide,polyether block amide or polyester block amide (PEBAX),polyetheretherketone (PEEK), polyethylene terephthalate (PET),polybutylene terephthalate (PBT), polyetherimide (PEI), polystyrene(PS), acetel, polymethylmethacrylate (PMMA or acrylic), nylon, Teflon,and polyvinyl chloride (PVC). Some of the factors that may influence theproper material include the dimensions of the flexible portion and theforces, pressures, and deformations that the flexible portion may besubjected to during use. The flexible portion 220, being hollow in oneembodiment, may have strength and modulus as the main limitations fordetermining a suitable flexible material. If the modulus or strength istoo low, then the wall may not be able to resist injection pressures(i.e., excessive deformation, compliance or rupture), or be unable toapply enough force to needle tip portion 210 to penetrate a body tissue(i.e., excessive compression or low compression modulus). Flexibleportion 220 may also break when subjected to a tortuous environmentand/or lack the ability to control needle tip portion 210 to desiredpenetration angles. Material modulus and strength interact. If themodulus is high enough to satisfy compression and/or compliance issues,then its strength must be proportionally as high to deal with ruptureand/or bending issues. These materials disclosed above may also be usedto impregnate a spring(s) and/or a braid(s) to form and/or reinforce theshaft. In one embodiment, sheath 250 may also be made of materialscomparable to flexible portion 220 because sheath 250 may need to bendand flex with needle 200.

Needle shaft 230, as part of the needle catheter coupled to flexibleportion 220 and tip portion 210, should possess flexible properties toadvance through a tortuous body lumen while providing sufficient supportsuch that it does not kink or collapse during this advancement or whenit is advanced relative to sheath 250 to cause tip portion 210 topenetrate body tissue. As such, needle shaft 230 may be bent during use,particularly near a distal end of needle 200. In one embodiment, needleshaft 230 may be made of polymers or polymer blends discussed above withrespect to flexible portion 220 of needle 200 in order to providesimilar flexural properties. Alternatively, needle shaft 230 may be madeof metallic or ceramic materials discussed above with respect to tipportion 210 of needle 200.

Shaft 230 is also flexible to limit the friction forces between it andsheath 250 when in a tortuous anatomy. If shaft 230 is not flexibleenough, then the forces during needle 200 advancement (relative tosheath 250) could stretch the catheter, shear/peal sheath 250 away fromthe catheter, break catheter/sheath bonds, compress the shaft (retardingpenetration) or make it very difficult to advance (cause penetration),as well as, retract. During retraction similar problems may occur,except the catheter/sheath bonds may be compressed.

As noted above, tip portion 210 is coupled to flexible portion 220 byforming a first overlapping joint 240. FIG. 3A and FIG. 3B illustrateneedles 300A and 300B having embodiments of overlapping joint structures330A and 330B between tip portions 310A, 310B and flexible portions320A, 320B. For clarity of description, needles 300A and 300B areillustrated without a sheath or needle shaft coupled to flexibleportions 320A, 320B. FIG. 3A illustrates overlap joint 330A formed byflexible portion 320A overlapping tip portion 310A. Outer diameter (OD)312A of tip portion 310A is smaller than inner diameter (ID) 322A (andalso outer diameter 321A) of flexible portion 320A of overlap joint330A. Alternatively, OD 312A of tip portion 310A may be substantiallysimilar to ID 322A of tip portion near a distal end of tip portion 310Abut tapers to a smaller OD near flexible portion 320A so as to fitinside of flexible portion 320A. In one embodiment, the two portions maybe bonded together with an adhesive (e.g., Loctite 4061). Comparableadhesives known in the art may also be used to bond tip portion 310A toflexible portion 320A to form overlap joint 330A. In one embodiment,overlap joint 330A may have a length of about 0.5 millimeters to providesufficient bonding area between tip portion 310A and flexible portion320A.

Alternatively, overlapping joint 330B may perform better when thebonding positions are reversed. As illustrated by FIG. 3B, flexibleportion 320B is placed inside tip portion 310B such that an outerdiameter 324B of flexible portion 320B is inside an inner diameter 314Bof tip portion 314B. Flexible portion 320B may have the lowest modulusor change its dimensions more in response to pressure on the ID when adrug is injected through flexible portion 320B, thereby subjectingoverlap joint 330B to a peel-type force that would separate tip portion310B from flexible portion 320B. In other words, flexible portion 320Bmay expand more and have a tendency to separate from tip portion 310B.If flexible portion 320B, made from a polymer or polymer blend asdiscussed above, is overlapped by tip portion 310B, the expansionflexible portion 320B at joint 330B, may be limited by the stiffer tipportion and the forces generated may have a tendency to seal overlapjoint 330B, rather than peel it apart. This may produce a more reliable,leak-proof joint 330B.

In one embodiment, in addition to the various polymers and polymerblends discussed above with respect to materials that may be used forthe flexible portion of a needle, flexible portions 320A, 320B may bereinforced with additional elements to exhibit suitable modulus and/orstrength properties. Dimensions being equal, a polymer flexible portionmay compress or elongate more than a metallic portion under the sameforces, thereby raising issues of needle longitudinal position controlwith a polymer flexible portion and/or needle shaft. This may bemitigated by the use of braids or springs within the polymer wall.Moreover, reinforcing flexible portions 320A, 320B increases theirresistance to kinking or buckling (i.e., compressive failure), eventsthat may compromise injection capability. FIGS. 4A and 4B illustrateflexible portions 420A and 420B and needle tip portions 410A and 410B ofneedles 400A and 400B embedded with reinforcing elements 422A and 424B,respectively. In another embodiment, the reinforcing elements may extendto the needle shaft (e.g., needle shaft 230 of FIG. 2). FIG. 4Aillustrates flexible portion 420A (e.g., made of a polymer or polymerblend) reinforced with very thin wire in a braided pattern 422A.Alternatively, FIG. 4B illustrates flexible portion 420B of need 400Breinforced with very thin wire in a coil or spring pattern 422B.

FIG. 5 illustrates one embodiment of distal tip 505 region of needlecatheter 500 having a flexible needle. Catheter body 510 encloses needlelumen 520 which extends from a proximal region (not shown) towardsdistal tip 505. Needle lumen 520, however, does not extend straighttowards distal tip 505. Needle lumen 520 angles upwards to needle lumenopening 522. This type of configuration for needle lumen 520 may beapplicable for penetrating a vessel wall after needle catheter 500 hasbeen advanced to a target treatment region (not shown). Needle tipportion 540 is illustrated retracted within needle lumen 520. Needle tipportion is coupled to flexible polymer portion 530 at one end by a firstoverlap joint 550. Flexible polymer portion is coupled to needle shaft525 at its other end by a second overlap joint 555. First overlap joint550 has needle tip portion 540 overlapping flexible polymer portion 530,and second overlap joint 555 has needle shaft 525 overlapping flexiblepolymer portion 530. In an alternative embodiment, either or bothoverlap may be reversed. As illustrated, flexible polymer portion 530 ofthe needle enables needle tip portion to bend at an angle upwardsrelative to the longitudinal length of catheter body 510. Needle lumen520 serves to guide needle tip portion 540 towards opening 522 such thatin an extended position, needle tip portion 540 may penetrate a bodytissue. The bend of flexible polymer portion 530 is illustrative of awide range of angles that may easily be achieved. A control handle (notshown) at the proximal end of needle catheter 500 is used to selectivelyextend and retract needle tip portion 540. Various depth sensors orcontrols may be used in this and other embodiments to sense and/orcontrol the depth of penetration of needle tip portion 540 into thetarget tissue.

FIG. 6 illustrates a cross sectional view of one embodiment of a needlecatheter for injecting a biologic agent or therapeutic drug into a bodytissue. In one embodiment, needle catheter 600 may have elongatedcatheter body 610 that surrounds needle lumen 612 and inner lumen 614.Housed within inner lumen 614 are fluid lumen 616 and inner member 618that also contains guide wire 622 within guide wire lumen (not shown).Inflatable balloon 626 is coupled to inner lumen 614 and the innermember 618. Proximal end 628 of balloon 626 is coupled to distal end 630of inner lumen 614 and distal end 632 of balloon 626 is coupled todistal end 636 of inner member 618.

In an alternative embodiment, both guide wire 622 and a retractableultrasonic element (not shown) may be housed within inner member 614.Elongate body 610 surrounds inner member 614 and needle lumen 612.Housed within inner lumen 614 are inner member 618 and fluid lumen 616.Inner member 618 surrounds guide wire 622. Inflatable balloon 626 iscoupled to inner lumen 614 and inner member 618. Proximal end 628 ofballoon 626 is coupled to distal end 630 of inner lumen 614 and distalend 632 of balloon 626 is coupled to distal end 636 of inner member 618.

As further illustrated in FIG. 6, retractable needle 613 is housed inneedle lumen 612 and freely movable therein. The hollow, tubular shapedneedle 613 in one embodiment, may have an inner diameter within a rangeof approximately 0.002 inch to 0.010 inch (5.1×10⁻³ cm to 25.4×10⁻³ cm)and an outer diameter within the range of approximately 0.004 inch to0.012 inch (10.2×10⁻³ cm to 30.5×10⁻³ cm). The hollow needle provides afluid channel that extends from proximal end 662 to a distal end ofneedle 613. Inflatable balloon 626, illustrated in an expanded state,bends needle lumen 612 along with needle 613 at an angle away frominflatable balloon 626. In one embodiment, needle 613 may have a radiusof curvature of about 30 degrees to 90 degrees. The flexibility ofneedle 613 facilitates placement of the needle tip near or within adesired target of a plaque or treatment region. As discussed above,needle 613 may be formed from a variety of metals including, but notlimited to stainless steel, NiTi or other comparable semi-rigid andrigid materials.

Referring again to FIG. 6, a proximal end of needle 613 may be coupledto adapter 650 that couples needle 613 to needle lock 652 and needleadjustment knob 654. Needle lock 652 is used to secure needle 613 inplace and prevent further movement of needle 613 within an arteriallumen once needle 613 is placed in the target position. Needleadjustment knob 654 controls accurate needle extension out of the distalend of the catheter and depth of penetration into the plaque or targettreatment region. As such, movement of needle adjustment knob 654 movesneedle 613 in and out of needle lumen 612. Once needle 613 haspenetrated a target to a desired depth, needle lock 652 enables needle613 to be secured in place thereby preventing any movement of needle 613within needle lumen 612.

A drug injection port 660 may be disposed near proximal end 662 ofneedle catheter 600. Drug injection port 660 couples needle catheter 600with various dispensing devices such as a syringe or fluid pump. Fluidsinjected into drug injection port 660 travel through needle 613 and aredispensed from the distal tip of needle 613.

FIGS. 7 and 7A illustrate cross-sectional views of another embodiment ofa needle catheter 700, in particular, a distal region having expandablemember 740 (e.g., an angioplasty-type balloon) that may control apenetration angle of dual needle assemblies 720, 730. Dual needles maybe an effective way to deliver a uniform dosage of a drug or bioactiveagent to a vessel wall because in many instances, a vessel growth orocclusion may be present all along the inner wall (e.g., around thecomplete circumference of an arterial wall). Moreover, a dual needlecatheter may reduce the number of percutaneous procedures necessary totreat a particular treatment region. The distal region of catheter 700has an end of catheter body 710 from which expandable member 740extends. In one embodiment, a guidewire lumen 750 (that may be formed bya tubing within catheter 700) may be present along a longitudinal lengthof catheter body 710 through expandable member 740. The distal end ofexpandable member 740 is sealed to the tubing forming guidewire lumen750. Inflation lumen 760 also extends from catheter body 710 toexpandable member.

Needle sheaths 722, 732 having lumens 770, 772 are disposed along asurface of expandable member 740 near its proximal end. Needle sheaths722, 732 conform to the shape of expandable member 740, illustrated inits expanded or inflated state. Needle 720, having tip portion 724coupled to flexible portion 728, is disposed within needle sheath 722. Aportion of needle shaft 780, coupled to flexible portion 728, may alsobe disposed within needle sheath 722. Needle tip portion 724 forms afirst overlapping joint 726 with flexible portion 728 and needle shaft780 forms a second overlapping joint 727. Similarly, Needle 730, havingtip portion 734 coupled to flexible portion 738, is disposed withinneedle sheath 732. A portion of needle shaft 782, coupled to flexibleportion 738, may also be disposed within needle sheath 732. Needle tipportion 734 forms a first overlapping joint 736 with flexible portion738 and needle shaft 782 forms a second overlapping joint 737. Needleshaft 780 and 782 extend back to and are coupled to a control handle ata proximal end of catheter 700, and the control handle allows theneedles to be selectively extended and retracted.

In an alternative embodiment, second overlapping joints 727, 737 may notbe present, such that flexible portion 728, 738 extend all the way to aproximal end of needle catheter 700. Additionally, as discussed above,flexible portions 728, 738 may be reinforced with braided, with a coiledwire or wires, or with combinations of coils and/or braids within itswalls. Needle tip portions 724, 734 may have two positions when in use.A first retracted position, as illustrated, has needle tip portions 724,734 completely housed within sheaths 722, 732. In this retractedposition, first overlapping joints 726, 736 should be positioned distalto the bend point of needle sheath 722, 732, that is, closer to theopenings of the needle sheaths. Because needle tip portions are rigid,they may most likely not bend if any part of needle tip portiontraverses the bend point of needle sheaths 722, 732 as expandable member740 increases in size (i.e., expands).

Flexible portions 728, 738 also limit the friction forces between needletip portions 724, 734 and sheaths 722, 732, respectively, because thisarea may be bent to direct the needles off-axis to the catheter andinto/through a vessel wall. This type of bend may be more tortuous(i.e., having a lower radius of curvature) than shafts 780, 782.Moreover, if flexible portions 728, 738 are not made more flexible thanneedle tip portions 724, 734, then the forces on needle sheaths 722, 732from needle assemblies 720, 730 may cause them to separate from thecatheter body and/or greatly deform at the bend point during needleassembly advancement (i.e., when expandable member 740 is inflated). Ifneedle sheaths 722, 732 are greatly deformed or separated from theseforces, then needles assemblies 720, 730 may not follow the angledictated by the shape of expandable member 740 in its path toward avessel wall during extension. Because the angle of needle tip portions724, 734 to a desired target region may be less, their paths may notlonger reach the same penetration depth into the vessel. This may resultin the operator of needle catheter 700 no longer having control toinject needle tip portions 724, 734 to the desired target region.

A flexible needle shaft (e.g., needle shafts 780, 782) may limit theforces between the needle sheaths (or catheter) and the needleassemblies (e.g., flexible needle portion 728 and needle tip portion724) from bending that may cause friction forces, making it difficult tocontrol the advancement/retraction of the needle assemblies. Forexample, if these forces are high, the needle assembly is harder toadvance and the advancement forces act as a tensile force on thecatheter causing it and the sheaths to stretch, preventing the needlefrom extending away from the catheter body as desired or designed. Thecatheter may get longer but the needle assembly, in compression at thesame level of force, tends to shorten, so the penetration depth isrelatively less. Because the catheter gets longer, injection positioncontrol and injection depth control may be compromised. In extremecases, the catheter may continue to stretch appreciably once the needlehas engaged the wall. Then, when the advancement is completed and nomore force is applied to the needle assembly (and hence to thecatheter/sheaths), the catheter may spring back to its original, shorterlength which may disengage the needle from the vessel wall, increase theneedle's penetration depth and/or further damage the vessel wall. Theneedle may be made smaller, but the flow resistance increasessignificantly (i.e., low flow rate) making it very difficult to makeinjections by hand/syringe within any reasonable time frame, even withlow compliance.

Referring to FIGS. 8A-8D, an exemplary method of delivering a biologicagent to a body tissue using a flexible needle catheter is illustrated.In one embodiment, needle catheter 800 may be comparable to needlecatheters 600 and 700 described in detail above with respect to FIGS. 6and 7. At FIG. 8A, a distal end 820 of needle catheter 800 is advancedthrough vessel lumen 805 to a target tissue region (e.g., vessel wall810). In one embodiment, needle catheter 800 may be an over-the-wiretype in which a guidewire lumen extends from a proximal end of needlecatheter 800 to a distal end, enabling needle catheter 800 to advanceover the guidewire to a location in vessel lumen 805 (e.g., of apatient). As an alternative to an over-the-wire catheter, a rapidexchange catheter delivery system may be utilized. As such, the cathetermay be any of the catheter types used in the art, including but notlimited to “rapid exchange” (RX) catheters, “over-the-wire” (OTW)catheters, or a “tip RX” catheters. To facilitate its passage throughvessel lumen 805, needle catheter 800 maintains a low profile, withexpandable balloon 840 in a collapsed state and needles (not shown) in aretracted position within needle sheaths 825, 830. At FIG. 8B, balloon840 begins to expand by passing an inflation medium through an inflationlumen (e.g., inflation lumen 760 from FIGS. 7 and 7A). The inflationmedium may be any type common in the art of balloon catheter technologyand angioplasty balloons (e.g., fluids, including gas and liquid). Asballoon 840 expands, needle sheaths 825, 830, disposed along a surfaceof balloon 840 near its proximal end, bends in the direction of vesselwall 810.

At FIG. 8C, balloon 840 has reached a desired inflation size such thatneedle sheaths 825, 830 point towards a target region of vessel wall 810which may be a coronary artery or an artery which supplies oxygen to thebrain. From here, needle tip portions 850, 855 advance past the openingof needle sheaths 825, 830 from a retracted position to an extendedposition to penetrate vessel wall 810. At FIG. 8D, biologically activeor therapeutic agents 860, 865 are delivered from a proximal end of thecatheter through needle tip portions 850, 855. Once a desired dosage ofbiologically active agents 860, 865 have been delivered to vessel wall810, needle tip portions 850, 855 are retracted back into needle sheaths825, 830, expandable balloon 840 is deflated, and the needle catheterremoved back through vessel lumen 805. The advantage of utilizing aneedle catheter having a flexible portion coupled to the needle tipportion is that the needle tip portions may be easily angled to a widerange of positions to target a vessel wall. The polymeric nature of theflexible portion coupled to the needle tip portion prevents kinkingduring both catheter advancement through a vessel lumen and penetrationof a body tissue. (e.g., vessel wall). To reinforce flexible polymerportion 825, 830, braided or coiled wire may be embedded within itswalls as described above.

FIG. 9 illustrates an exemplary method of delivering a biologic agent toan intraventricular wall of the heart with one embodiment of a flexibleneedle catheter assembly 900 of the present invention. Needle 910 isshown in its distal most, extended position and penetrating myocardium902. The distal end of the modified guiding catheter 920 is shownresident in left ventricle 904 and aorta 906, although it may beappreciated that other insertion sites for the needle catheter may bechosen to access the other chambers of the heart, if desired. At anextreme distal end of guide 920 is articulating section 925, which canbe deflected into a number of curved positions. Guiding catheter's 920ID and needle catheter 930 OD may be chosen such that needle catheter930 is extendable out of guiding catheter 920. The curve of articulatingsection 925 directs needle catheter 930 toward the desired area ofmyocardium 902. Dotted line structure 926 is a representation ofarticulating section 925 and needle catheter 930 in a relativelystraight position. By advancing or retracting guide catheter 920 andadjusting the curvature of its articulating section 925, retractedneedle catheter 930 may be advanced into contact with all areas of themyocardium 902 along a line up the left side of ventricle 904, such thatneedle 910 may penetrate myocardium 902 at a high angle (in the vicinityof 60°-90°) to ensure an adequate depth of penetration. By rotatingguide catheter 920, this line may be swept such that all areas ofmyocardium 902 within ventricle 904 may be accessed in this manner. Inone embodiment, distal end of guide 920 and needle catheter 930 beradiopaque, such that they may be observed under fluoroscopy. In anotherembodiment, guide 920 may be made 8 F or smaller and still accommodateneedle shaft 930.

For the type of use described with respect to FIG. 9 (i.e.,intra-cardiac drug delivery), size constraints for needle catheter 900may not be as severe compared to a needle catheter used for drugdelivery within a tortuous vessel lumen. As such, needle shaftdimensions may be chosen to be larger (OD/ID/wall thickness), but highflexibility may still be desired to facilitate guide insertion and/orplacement and guide tip deflection. High flexibility may also be desiredto limit the contact pressure of needle catheter 930 against the cardiacwall, to prevent trauma, arrhythmia, or both. A larger ID for needlecatheter 930 causes the flow resistance to be reduced dramatically inneedle catheter 930, so compliance issues may be mitigated. A fulllength, polymer shaft (as opposed to a metallic shaft or combinationpolymer/metallic shaft) may be more practical, in which case the needleshaft may contain a braid(s) and/or spring(s) to improve compression,burst strength and compliance properties. Polymer blends that may beadhered to the braid(s) and/or spring(s) include for example, PRIMACORcopolymers.

As noted above, compliance may be an issue in high flow resistance tubes(e.g., needle catheter 700 of FIG. 7). Compliance is the change in lumenvolume per unit change in lumen pressure. As the flow resistanceincreases, the pressure is proportionally higher at any point in thelumen at any give flow rate. Thus, during injection by an operator inhigh flow resistance tubes and/or high compliance tubes, part of theinjected material volume fills the increasing volume of the lumen (i.e.,injectate is stored by the expanding lumen). After injection, thepressure begins to drop and the lumen begins to return to its normalvolume, slowly squeezing out the rest of the injected material againstthe flow resistance of the needle assembly. Thus, even though theoperator may have injected the material very rapidly into the proximalend of the needle catheter, the material may flow very slowly out of thedistal end of the needle assembly for an extended period of time with anincreasing and then decreasing flowrate. The actual injection time canbecome relatively long and be very different from that perceived by anoperator. This may result in long treatment times and/or the prematureretraction of the needle assembly prior to the proper dose beingdelivered.

If the flow resistance is low, then the pressure in the lumen may be lowand very little injectate is stored during injection and, afterinjection, the stored injectate is rapidly expelled because the low flowresistance enables it to leave rapidly (or the stored injectate volumebecome negligible). If the compliance is low, then little injectate isstored in the lumen, regardless of the pressure, and it may take verylittle time to expel the injectate, regardless of the flow resistance.

In the foregoing specification, the invention has been described withreference to specific exemplary embodiments thereof. It will, however,be evident that various modifications and changes may be made theretowithout departing from the broader spirit and scope of the invention asset forth in the appended claims. The specification and drawings are,accordingly, to be regarded in an illustrative rather than a restrictivesense.

1. A catheter, comprising: an elongated tubular member having a proximalend and a distal end; and an expandable member having a shoulder regiondisposed near the distal end of the elongated tubular member; a needledisposed in a needle lumen over the shoulder region of the expandablemember near the distal end, the needle comprising a rigid, penetratingtip coupled to a flexible portion by an overlapping joint, wherein theflexible portion enables the needle to bend to a penetrating anglecontrolled by an angle of the shoulder region relative to the distal endof the elongated tubular member upon expansion of the expandable memberand penetrate a body tissue without kinking, wherein the needle ismovable within the needle lumen.
 2. The catheter of claim 1, furthercomprising a flexible needle sheath that is coupled adjacent to theshoulder region of the expandable member disposed over the needle,wherein the needle remains within the needle sheath in a retractedposition, and extends out of the needle sheath in a penetratingposition.
 3. The catheter of claim 1, wherein the overlapping joint hasthe rigid, penetrating tip disposed over the flexible portion.
 4. Thecatheter of claim 1, wherein the overlapping joint has the flexibleportion disposed over the rigid, penetrating tip.
 5. The catheter ofclaim 1, wherein the flexible portion that forms the overlapping jointwith the rigid, penetrating tip is reinforced with a metallic materialdisposed within the flexible portion.
 6. The catheter of claim 5,wherein the metallic material forms a wire mesh within the flexibleportion.
 7. The catheter of claim 5, wherein the metallic material formsa coil within the flexible portion.
 8. The catheter of claim 1, whereinthe rigid, penetrating tip is made from stainless steel.
 9. The catheterof claim 1, wherein the rigid, penetrating tip is made fromnickel-titanium (NiTi).
 10. The catheter of claim 1, wherein the rigid,penetrating tip is made from a ceramic material.
 11. The catheter ofclaim 1, wherein the flexible portion is selected from a groupconsisting of polyimide, polyether block amide or polyester block amide(PEBAX), polyetheretherketone (PEEK), polyethylene terephthalate (PET),polybutylene terephthalate (PBT), polyetherimide (PEI), polystyrene(PS), acetel, polymethylmethacrylate (PMMA or acrylic), nylon, Teflon,and polyvinyl chloride (PVC).
 12. A catheter, comprising: an elongatedtubular member; a needle shaft disposed within a lumen of the elongatedtubular member, the needle shaft having a proximal portion and a distalportion; an expandable member having a shoulder region disposed near thedistal portion of the needle shaft; and a needle coupled to the distalportion of the needle shaft, the needle positioned adjacent and over theshoulder region of the expandable member, the needle comprising apolymeric tube portion coupled to a rigid tip portion by a firstoverlapping joint, wherein the polymeric tube portion enables the needleto bend to a penetration angle determined by an angle of the shoulderregion upon expansion of the expandable member and penetrate a bodytissue without kinking.
 13. The catheter of claim 12, further comprisinga needle sheath to house the needle, when the needle is in a retractedposition.
 14. The catheter of claim 12, wherein the needle shaftcomprises a metallic material, wherein the distal portion of the needleshaft is coupled to the polymeric tube portion by a second overlappingjoint.
 15. The catheter of claim 12, wherein the needle shaft comprisesa polymeric material, wherein the distal portion of the needle shaft iscoupled to the polymeric tube portion by a second overlapping joint. 16.The catheter of claim 12, wherein the first overlapping joint has therigid, tip portion disposed over the polymeric tube portion.
 17. Thecatheter of claim 12, wherein the first overlapping joint has thepolymeric tube portion disposed over the rigid, tip portion.
 18. Thecatheter of claim 12, wherein the polymeric tube portion that forms thefirst overlapping joint with the rigid, tip portion is reinforced with ametallic material disposed within the polymeric tube portion.
 19. Thecatheter of claim 18, wherein the metallic material forms a wire meshwithin the polymeric tube portion.
 20. The catheter of claim 18, whereinthe metallic material forms a coil within the polymeric tube portion.21. The catheter of claim 12, wherein the rigid, tip portion is madefrom stainless steel.
 22. The catheter of claim 12, wherein the rigid,tip portion is made from nickel-titanium (NiTi).
 23. The catheter ofclaim 12, wherein the rigid, tip portion is made from a ceramicmaterial.
 24. The catheter of claim 12, wherein the polymeric tubeportion is selected from a group consisting of: polyimide, polyetherblock amide or polyester block amide (PEBAX), polyetheretherketone(PEEK), polyethylene terephthalate (PET), polybutylene terephthalate(PBT), polyetherimide (PEI), polystyrene (PS), acetel,polymethylmethacrylate (PMMA or acrylic), nylon, Teflon, and polyvinylchloride (PVC).
 25. A catheter of claim 12, wherein the expandablemember comprises a balloon.
 26. The catheter of claim 12, wherein theneedle shaft has a lumen to deliver a biologic agent through the needle.27. A catheter, comprising: an elongated tubular member having aproximal end and a distal end; and an expandable member having ashoulder region disposed near the distal end of the elongated tubularmember; a needle disposed in a needle lumen near the distal end, theneedle comprising a rigid, penetrating tip coupled to a flexible portionthe needle being movable within the needle lumen; and means for bendingthe needle to a penetration angle, wherein the flexible portion enablesthe needle to bend to the penetration angle controlled by an angle ofthe shoulder region relative to the distal end of the elongated tubularmember upon expansion of the expandable member and penetrate a bodytissue without kinking.
 28. The catheter of claim 27, furthercomprising: a needle shaft coupled to the flexible portion; and meansfor bending a second needle to a second penetration angle.
 29. Thecatheter of claim 27, further comprising means for reinforcing theflexible portion with a braided wire.
 30. The catheter of claim 27,further comprising means for reinforcing the flexible portion with acoiled spring.